Prognostic value of N-terminal Pro–B-Type natriuretic peptide in patients with intermediate coronary lesions

BackgroundThe optimal treatment strategy for patients with coronary intermediate lesions, defined as diameter stenosis of 50–70%, remains a great challenge for cardiologists. Identification of potential biomarkers predictive of major adverse cardiovascular events (MACEs) risk may assist in risk stratification and clinical decision.MethodsA total of 1,187 patients with intermediate coronary lesions and available N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were enrolled in the current study. A baseline NT-proBNP level was obtained. The primary endpoint was defined as MACEs, the composite endpoint of all-cause death and non-fatal myocardial infarction. A multivariate Cox regression model was used to explore the association between NT-proBNP level and MACE risk.ResultsThe mean age of the study cohort was 59.2 years. A total of 68 patients experienced MACE during a median follow-up of 6.1 years. Restricted cubic spline analysis delineated a linear relationship between the baseline NT-proBNP level and MACE risk. Both univariate and multivariate analyses demonstrated that an increased NT-proBNP level was associated with an increased risk of MACE [adjusted hazard ratio (HR) per doubling: 1.412, 95% confidence interval (CI): 1.022–1.952, p = 0.0365]. This association remains consistent in clinical meaningful subgroups according to age, sex, body mass index (BMI), and diabetes.ConclusionAn increased NT-proBNP level is associated with an increased risk of MACE in patients with intermediate coronary lesions and may serve as the potential biomarker for risk stratification and treatment decision guidance

Ignition temperature and explosion pressure of suspended coal dust cloud under different conditions and suppression characteristics

Abstract The ignition and explosion processes of suspended coal dust clouds and their suppression characteristics are important aspects of dust prevention and control. To understand the ignition temperature and explosion pressure of coal dust clouds, as well as the inhibitory effect of explosion suppressants, experimental tests are conducted. The study found that during the ignition process of coal dust clouds, the optimal dust spray pressure is 20 kPa, because coal dust clouds are more likely to ignite under this condition. When the mass concentration of coal dust cloud is 500 g m−3, the maximum pressure and maximum pressure rise rate are both the highest. When Al(OH)3 is mixed with coal dust and the mass percentage is 60%, the coal dust cloud can still be ignited. When KH2PO4 is mixed with coal dust, the upper limit of the test temperature is reached when the percentage of mixture is 55%. When NH4H2PO4 is mixed with coal dust and the mass percentage is greater than 40%, the coal dust cloud can’t be ignited anymore. The suppression effect of mixing Al(OH)3 and NH4H2PO4 is not as good as that of mixing KH2PO4 and NH4H2PO4

Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications

Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.Published versionThis work was supported by the National Natural Science Foundation of China (No. 81974502 and 81671293), the Natural Science Foundation of Hunan Province (No. 2020JJ3061, China), andthe Hunan Provincial Department of Education Innovation Platform Open Fund Project (No. 17K100, China)

γ-Core Guided Antibiotic Design Based on Human Enteric Defensin 5

An increase in the number of infections caused by resistant bacteria worldwide necessitates the development of alternatives to antibiotics. Human defensin (HD) 5 is an innate immune peptide with broad-spectrum antibacterial activity, but its complicated structure makes its preparation difficult. Herein, we truncated the HD5 structure by extracting the highly conserved γ-core motif. A structure-activity study showed that this motif was ineffective in killing bacteria in the absence of specific spatial conformation. Notably, after the introduction of two intramolecular disulfide bonds, its antibacterial activity was markedly improved. Glu and Ser residues were then replaced with Arg to create the derivative RC18, which exhibited stronger potency than HD5, particularly against methicillin-resistant S. aureus (MRSA). Mechanistically, RC18 bound to lipid A and lipoteichoic acid at higher affinities than HD5. Furthermore, RC18 was more efficient than HD5 in penetrating the bacterial membranes. Molecular dynamics simulation revealed that five Arg residues, Arg1, Arg7, Arg9, Arg15, and Arg18, mediated most of the polar interactions of RC18 with the phospholipid head groups during membrane penetration. In vivo experiments indicated that RC18 decreased MRSA colonization and dramatically improved the survival of infected mice, thus demonstrating that RC18 is a promising drug candidate to treat MRSA infections